Eletriptan in the management of acute migraine. An update on the evidence for efficacy, safety, and consistent response

Migraine is a multifactorial, neurological and disabling disorder, also characterized by several autonomic symptoms. Triptans, selective serotonin 5-HT1B/1D agonists, are the first-line treatment option for moderate-to-severe headache attacks. In this paper, we review the recent data on eletriptan clinical efficacy, safety, and tolerability, and potential clinically relevant interactions with other drugs. Among triptans, eletriptan shows a consistent and significant clinical efficacy and a good tolerability profile in the treatment of migraine, especially for patients with cardiovascular risk factors without coronary artery disease. It shows the most favorable clinical response, together with sumatriptan injections, zolmitriptan and rizatriptan. Additionally, eletriptan shows the most complex pharmacokinetic/dynamic profile compared with the other triptans. It is metabolized primarily by the CYP3A4 hepatic enzyme and therefore the concomitant administration of CYP3A4-potent inhibitors should be carefully evaluated. A relatively low risk of serotonin syndrome is given by the co-administration with serotoninergic drugs. No clinically relevant interaction has been found with drugs used for migraine prophylactic treatment or other acute drugs, with the exception of ergot derivatives that should not be co-administered with eletriptan

Bienestar y calidad de vida relacionada con la salud en una muestra urbana de jóvenes

En esta tesis se analiza la relación entre las variables sociodemográficas y los estilos de vida y su influencia en la calidad de vida de los jóvenes residentes en el barrio de Casablanca (Zaragoza). Se consideran los factores que la Comisión de los Determinantes Sociales de la Salud (OMS) tiene en cuenta para explicar nuestro nivel de salud, como por ejemplo el sexo, la edad, el nivel de instrucción, la situación laboral, el nivel de ingresos, la zona de residencia, los comportamientos de ocio y tiempo libre, y las conductas saludables y/o de riesgo. La definición de calidad de vida relacionada con la salud se corresponde con la propuesta dada por la OMS en 1993 y su operativización en el cuestionario WHOQOL: la percepción del individuo de su posición ante la vida en el contexto de la cultura y del sistema de valores en el que se vive. La muestra de esta investigación se compone de 245 jóvenes del barrio de Casablanca (Zaragoza) estratificada según el sexo (hombres y mujeres), la zona de residencia (Viñedo Viejo, las Nieves y Fuentes Claras) y la edad (de 15 a 29 años), con un nivel de confianza del 90% y un margen de error ± 5. Para analizar los datos se han utilizado técnicas estadísticas descriptivas e inferenciales. Los resultados reflejan como la calidad de vida relacionada con la salud en los jóvenes no se distribuye por igual. En este sentido, el nivel educativo del encuestado resultó ser una de las variables con mayor valor predictivo. En las conclusiones se comentan los resultados más relevantes -y se aportan nuevas líneas de investigación. Con este estudio se pretende orientar futuros proyectos relacionados con programas socio educativos y entornos saludables, cuyos protagonistas son los jóvenes y la comunidad en la que se integran. Esta tesis forma parte de los trabajos realizados por el grupo de investigación "Bienestar y Capital Social" de la Universidad de Zaragoza, sobre los factores de riesgo y determinantes sociales de la salud, en el proyecto de investigación I+D+I (CSO 2011¬30089): "Comportamiento sexual y reproductivo en España: factores de riesgo para la salud", subvencionado por el Ministerio de Ciencia e Innovación

Gene variants with suicidal risk in a sample of subjects with chronic migraine and affective temperamental dysregulation

BACKGROUND: Risk factors for suicide are at least partially heritable and functional polymorphisms of targeted genes have been suggested to be implicated in the pathogenesis of this phenomenon. However, other studies examining the association between specific gene variants and suicide revealed inconsistent findings. We aims to evaluate the possible association between MAO-A3, CYP1A2*1F and GNB3 gene variants, hopelessness and suicidal risk in a sample of subjects with chronic migraine and affective temperamental dysregulation. METHODS: 56 women were genotyped for MAO-A3, CYP1A2*1F and GNB3 gene variants. Participants were also assessed using Beck Hopelessness Scale (BHS), the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A), and the Suicidal History Self-Rating Screening Scale (SHSS). RESULTS: Patients with higher total scores on affective dysregulated temperaments are more likely to have higher BHS (11.27 +/- 5.54 vs. 5.73 +/- 3.81; t19.20 = -3.57; p = 9 indicating high levels of hopelessness. No association was found between MAO-A3, CYP1A2*1F and GNB3 gene variants and suicidal risk as assessed by BHS and SHSS. CONCLUSIONS: This study did not sustain the association between MAO-A3, CYP1A2*1F and GNB3 gene variants and increased suicidal risk in patients with chronic migraine and affective temperamental dysregulation. Further studies investigating the gene-environment interaction or focusing on other genetic risk factors involved in suicidal behaviour are needed

Validation of a small-size pooling approach targeting hospital surveillance of SARS-CoV-2 infection

Recent studies describing the detection of SARS-CoV-2 RNA in pools of 5 to 32 samples reported false negative rates up to 10% for large groups, suggesting that smaller sample pools are a good compromise to increase sample processing capacity while maintaining test reliability. Since 5-sample pools were shown to efficiently detect SARS-CoV-2 RNA in RT-PCR assays, we chose to test and validate this approach using a highthroughput RNA extraction and amplification platform

Degradation rate of 5-fluorouracil in metastatic colorectal cancer. A new predictive outcome biomarker?

BACKGROUND: 5-FU based chemotherapy is the most common first line regimen used for metastatic colorectal cancer (mCRC). Identification of predictive markers of response to chemotherapy is a challenging approach for drug selection. The present study analyzes the predictive role of 5-FU degradation rate (5-FUDR) and genetic polymorphisms (MTHFR, TSER, DPYD) on survival. MATERIALS AND METHODS: Genetic polymorphisms of MTHFR, TSER and DPYD, and the 5-FUDR of homogenous patients with mCRC were retrospectively studied. Genetic markers and the 5-FUDR were correlated with clinical outcome. RESULTS: 133 patients affected by mCRC, treated with fluoropyrimidine-based chemotherapy from 2009 to 2014, were evaluated. Patients were classified into three metabolic classes, according to normal distribution of 5-FUDR in more than 1000 patients, as previously published: poor-metabolizer (PM) with 5-FU-DR ≤ 0,85 ng/ml/106 cells/min (8 pts); normal metabolizer with 0,85 < 5-FU-DR < 2,2 ng/ml/106 cells/min (119 pts); ultra-rapid metabolizer (UM) with 5-FU-DR ≥ 2,2 ng/ml/106 cells/min (6 pts). PM and UM groups showed a longer PFS respect to normal metabolizer group (14.5 and 11 months respectively vs 8 months; p = 0.029). A higher G3-4 toxicity rate was observed in PM and UM, respect to normal metabolizer (50% in both PM and UM vs 18%; p = 0.019). No significant associations between genes polymorphisms and outcomes or toxicities were observed. CONCLUSION: 5-FUDR seems to be significantly involved in predicting survival of patients who underwent 5-FU based CHT for mCRC. Although our findings require confirmation in large prospective studies, they reinforce the concept that individual genetic variation may allow personalized selection of chemotherapy to optimize clinical outcomes

Clostridium difficile outbreak: epidemiological surveillance, infection prevention and control

INTRODUCTION: Clostridium difficile infection (CDI) is currently considered the most common cause of health care-associated infections. The aim is to describe the trend of CDI in an Italian hospital and to assess the efficacy of the measures adopted to manage the burden. METHODS: we looked at CDI from 2016 to 2018. The incidence rate of CDIs was calculated as the number of new infected persons per month by the overall length of stay (incidence per 10,000 patient-days). Changes in the CDI rate during the period considered were analysed using a joinpoint regression model. RESULTS: thanks to the monitoring activity it was possible to adopt a new protocol, in order to manage CDI: the CDI episodes decreased from 85 in 2017 to 31 in 2018 (63% decrease). The joinpoint regression model was a useful tool to identify an important decrement during 2017, statistically significant (slope=-15.84; p= 0.012). CONCLUSIONS: reports based on routine laboratory data can accurately measure population burden of CDI with limited surveillance resources. This acitivity can help target prevention programs and evaluate their effect

Liver Cirrhosis Patients Homozygous for MTHFR C677T Develop Portal Vein Thrombosis 8 Years Earlier Than Wild Type

Background and Aim Age at portal vein thrombosis (PVT) in liver cirrhosis (LC) carriers of the methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C -&gt; T667 transition) polymorphism has never been addressed; we compared age at PVT in LC patients genotyped for the MTHFR and explored the interrelated clinical and laboratory factors predicting age at PVT. Approach and Results Retrospective cross-sectional cohort study. PVT participants: MTHFR CC n = 36, MTHFR CT n = 53, MTHFR TT n = 19; age, sex, age at PVT, Child-Pugh score, rs1799963 PT polymorphisms (G -&gt; A 20,210 transition), plasma HC and natural anticoagulants available for all participants. Age at PVT was lower in MTHFR TT than CT and CC (56 +/- 13 vs. 57 +/- 13 vs. 64 +/- 9 years, p = 0.001); median (IQR) plasma HC was higher in MTHFR TT than in the other groups [(17 (9.4, 23.3) vs 13 (8,14.7) vs 11 (8.9, 12.7) mu mol/l, p = 0.03)]. MTHFR TT, male gender and protein C predicted age at PVT (p = 0.02, p = 0.04 and p = 0.08); MTHFR TT and Child-Pugh score predicted plasma HC (p = 0.005 and p = 0.01) as well as low plasma protein C (p &lt; 0.0001 and p = 0.0002). Plasma HC inversely related to protein C in the MTHFR TT group (p &lt; 0.0001). Compound MTHFR TT with PT GA had lower age at PVT compared to MTHFR TT alone (49 +/- 18 vs 58 +/- 12 years). Conclusions MTHFR TT anticipates PVT associated with LC by an average of 8 years; MTHFR TT associates with severity of liver disease and to high plasma HC; the latter may contribute to the prematurity of PVT by interfering with the anticoagulant activity of protein C

Severe and prolonged myelosuppression during concomitant temozolomide and radiotherapy treatment in a patient with glioblastoma multiforme

Aims: We describe the case of a patient with glioblastoma (GBM) who developed severe and prolonged myelosuppression during concomitant daily temozolomide (TMZ) and radiotherapy (RT) treatment. Analysis of polymorphisms in genes correlated with TMZ-induced myelotoxicity was also performed. Presentation of the Case: A 67–year-old man with diagnosis of GBM undergoing concomitant RT-TMZ treatment developed severe and prolonged pancytopenia that led to discontinuation of TMZ and required frequent platelet and red cells transfusions. Analysis of single nucleotide polymorphisms (SNPs) in the genes NAD(P)H dehydrogenase, quinone 1 (NQO1) and glutathione S-transferase pi 1 (GSTP1) was carried out. Both SNPs were found to be wild-type. Discussion: TMZ is an oral alkylating agent used for the treatment of glioblastoma. TMZ is usually considered well tolerated and safe, with nausea and mild myelosuppression being the most common side effects. However, severe haematologic adverse events have been also reported. Recently, there has been growing interest in gene polymorphisms that might be associated with an increased risk of hematologic toxicity. Conclusion: Myelosuppression is a side effect that can occur relatively early during concomitant TMZ treatment and can negatively impact on patient’s quality of life. Further studies are warranted to find out a correlation between genetic factors and the occurrence of severe hematologic toxicity